Basiliximab Induction Therapy Research Articles

Successful A2 to O Simultaneous Liver and Kidney Transplantation in the Setting of Pre-operative Positive HLA Crossmatch: A Case Report

Simultaneous liver and kidney transplantation (SLKT) is possible for patients with high donor-specific HLA antibodies or with A2 donors to O recipients with high A2 titers. We report the first case of SLKT in a highly sensitized O recipient with organs from an A2 donor. The recipient is a 59-year-old woman with chronic kidney disease and liver failure due to autoimmune hepatitis and drug-induced liver injury. Immune work-up 8 days pre-transplant demonstrated a negative crossmatch and no HLA antibody (calculated panel reactive antibodies = 0%). Anti-A2 IgG levels were 512. The donor was a deceased 24-year-old man. One day before transplantation, serum from the recipient showed a significant increase in antibody reactivity (calculated panel reactive antibodies = 100%) attributable to blood product transfusion and memory response from previous pregnancies. Consequently, a crossmatch was positive for T and B cells with two newly detected HLA antibodies against the donor's antigens. On the day of surgery, the liver was transplanted first. Six hours and 37 minutes later, a repeat flow crossmatch was negative; donor-specific antibodies (DSAs) fell below the positive threshold, and anti-A2 IgG titer fell to 256. Thus, the kidney was transplanted after basiliximab induction therapy. Seven days post-transplant, non-donor-specific HLA antibodies were present but DSAs remain negative. The patient was discharged on postoperative day 57 with no signs of rejection at 4 months. This case illustrates a rapid and prolonged reduction in antibody titers (HLA and ABO) after SLKT. SLKT is feasible in patients with both DSA and high anti-A2 titer.

A comparative analysis of kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction: AUNOS database study.

The relative safety and efficacy of early steroid withdrawal in kidney transplant patients after basiliximab compared to anti-thymocyte globulin (ATG) induction therapy is unknown. We aimed to compare kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction from the United Network for Organ Sharing (UNOS) database. We conducted a retrospective cohort analysis of the UNOS database and included first kidney transplant recipients who received ATG or basiliximab induction therapy. We compared graft and patient outcomes in those who received steroid maintenance and those who were discharged off steroids. Of 106,061 patients, 25,344 (86.7%) received basiliximab induction and were maintained on steroids (B-Sm), and 3,880 (13.3%) were on a steroid-free regimen (B-Sf). Graft failure rate was significantly higher in the B-Sf compared to B-Sm at 1-year (4.1 vs. 1.8%, p<0.001), 3-year (6.0 vs. 4.3%, p<0.001) and 5-year follow-up (7.7 vs. 6.4%, p=0.0004). The mortality rate was significantly higher in B-Sf at 1-year (3.3 vs. 2.4%, p=0.0005), 3-year (7.6 vs. 5.5%, p<0.001) and 5-year follow-up (11.5 vs. 8.8%, p<0.001) when compared to the B-Sm. 76,837 recipients received ATG induction therapy, 51,745 (72.4%) were on steroid maintenance therapy (A-Sm) and 25,092 (32.6%) were on a steroid-free regimen (A-Sf). The graft failure rate was significantly higher in A-Sf compared to A-Sm at 1-year follow-up (2.6 vs. 2.3%, p=0.0006), however, there was no difference at 3-year (5.0 vs. 5.0%, p=0.53) or 5-year follow-up (7.2 vs. 8.1%, p=0.17). There was no difference in mortality rates between A-Sf vs. A-Sm at 1 year (2.5 vs. 2.4%, p=0.98) and at 3 years (5.5 vs. 5.4%, p=0.45), respectively. Patients who were maintained on steroids after basiliximab induction had better 5-year allograft survival and patient survival compared to those who were not maintained on steroids. However, steroid maintenance conferred no additional benefit after ATG induction and was associated with higher mortality.

(715) - The Influence of Basiliximab Induction Therapy on the Early Postoperative Outcomes / on Acute Cellular Rejection of Heart Transplant Recipients

(715) - The Influence of Basiliximab Induction Therapy on the Early Postoperative Outcomes / on Acute Cellular Rejection of Heart Transplant Recipients

Efficacy and safety of single-dose anti-thymocyte globulin versus basiliximab induction therapy in pediatric kidney transplant recipients: A retrospective comparative cohort study.

This study aimed to compare the efficacy and safety of basiliximab (BAS) versus a single dose of anti-thymocyte globulin (r-ATG) induction therapy in pediatric kidney transplant recipients (KTRs). This single-center retrospective comparative cohort study included all pediatric KTRs from May 2013 to April 2018 and followed up to 12 months. In the first period, all recipients received BAS, while from May 2016, a single 3 mg/kg dose of r-ATG was instituted. Maintenance therapy consisted of a calcineurin inhibitor plus prednisone plus azathioprine or mycophenolate. A total of 227 patients were included (BAS, n = 113; r-ATG, n = 114). The main combination of immunosuppressive drugs was tacrolimus, prednisone, and azathioprine in both groups (87% vs. 88%, p = .718). Patients receiving r-ATG showed superior survival-free of the composite endpoint (acute rejection, graft loss, or death; 76% vs. 61%, p = .003; HR 2.08, 1.29-3.34, p = .003) and lower incidence of biopsy-proven acute rejection (10% vs. 21%, p = .015). There was no difference in the overall incidence of CMV infection (33% vs. 37%, p = .457), PTLD (1% vs. 3%, p = .309), 30-day hospital readmissions (24% vs. 23%, p = .847), and kidney function at 12 months (86 ± 29 vs. 84 ± 30 mL/min/1.73m2, p = .614). These data suggest that induction therapy with a single 3 mg/kg dose of r-ATG is associated with higher efficacy for preventing acute rejection and similar safety profile compared to BAS.

Outcomes of older Black renal transplant recipients receiving basiliximab induction and early steroid withdrawal

AbstractThe efficacy and safety of early steroid withdrawal (ESW) in Black renal transplant recipients (RTR) remains uncertain, especially when combined with non‐lymphocyte depleting induction. This study compared patient and graft outcomes of older Black and Non‐Black RTR who received basiliximab induction followed by ESW.Included subjects in this single center, retrospective study were first‐time deceased and living donor RTR aged over 65 years who received basiliximab induction therapy and ESW. Black RTR and Non‐Black deceased donor RTR received an oral prednisone taper starting POD3 which was discontinued by POD21 per protocol.Of 139 patients (55 Black and 84 Non‐Black), the Black patient group included a higher percentage of deceased donors and hepatitis C positive donors, and more frequently underwent renal replacement therapy prior to transplant. One Black and zero Non‐Black RTR experienced graft loss within 3 years (p = 1.0). Patient survival was similar at 1 year (93% vs. 97%, p = .16) and 3 years (91% vs. 96%, p = .17). Rejection‐free survival and biopsy‐proven rejection did not differ at 1 or 3 years. Median eGFR and change in eGFR also did not differ between groups. Black patients were maintained on significantly higher median mycophenolate doses from 6 months post‐transplant to the end of the study period (p = .03 and .048).In older Black RTR, basiliximab induction followed by ESW produced comparable patient, graft, and rejection‐free survival compared to Non‐Black RTR over 3 years post‐transplant.

Excellent efficacy and beneficial safety during observational 5-year follow-up of rapid steroid withdrawal after renal transplantation (Harmony FU study).

We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled 1-year "Harmony" trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared with standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil and corticosteroids. The 5-year post-trial follow-up (FU) data were obtained in an observational manner at a 3- and a 5-year visit only for those Harmony patients who consented to participate and covered clinical events that occurred from the second year onwards. Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of RSWD. Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95% confidence interval 0.314-0.976; P=.041).The reduced incidence of post-transplantation diabetes mellitus in RSWD patients during the original 1-year study period was not compensated by later incidences during FU. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor-specific antibody formation or kidney function did not differ during FU period. With all the limitations of a post-trial FU study, the Harmony FU data confirm excellent efficacy and beneficial safety aspects of RSWD under modern immunosuppressive therapy over the course of 5 years after kidney transplantation in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients. Trial registration: Clinical trial registration number: Investigator Initiated Trial (NCT00724022, FU study DRKS00005786).

#3973 EXCELLENT EFFICACY AND BENEFICIAL SAFETY DURING FIVE YEAR FOLLOW-UP OF RAPID STEROID WITHDRAWAL AFTER RENAL TRANSPLANTATION (HARMONY STUDY)

Abstract Background and Aims We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal in the randomized controlled one year “Harmony” trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared to standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil, and corticosteroids. The five-year post-trial follow-up (FU) data reported here were obtained in an observational manner to evaluate, how these excellent short-term surrogate parameters will translate into hard long-term outcome parameters like patient death/graft loss. Method The five-year post-trial follow-up data were obtained in an observational manner at a three and a five-year visit for patients who consented to participate and covered clinical events that occurred from the second year onwards. Results Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of rapid steroid withdrawal (see Figure 1). Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95 % confidence interval 0.314 to 0.976; p = 0.041, see Table 1). The reduced incidence of post-transplantation diabetes mellitus in rapid steroid withdrawal patients during the original one-year study period was not compensated by later incidences during follow-up. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor specific antibody formation, or kidney function did not differ during follow-up period. Conclusion The Harmony follow-up trial confirms excellent efficacy and beneficial safety aspects of rapid steroid withdrawal under modern immunosuppressive therapy demonstrating for the first time increased patient survival in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients.

Outcomes after anti-thymocyte globulin vs Basiliximab induction before deceased donor kidney transplants

BackgroundDeceased donor kidney transplants represent an important source of renal replacement for the 100 000 patients initiating hemodialysis annually. We compared the association of induction therapy, anti-thymocyte globulin [rabbit] (rATG) or basiliximab, with posttransplant rejection, graft and patient survival. MethodsUsing the United Network for Organ Sharing (UNOS) database, we identified patients that received deceased donor kidney transplants. The outcomes analyzed were 6- month rejection, 1-year rejection, patient survival and graft survival. Multivariate logistic regression models were constructed to understand the association of induction therapy and rejection. Cox-proportional hazards models were constructed to ascertain the association of choice of induction therapy with both patient and graft survival. ResultsOf 45 339 patients, 33 906 patients received rATG induction therapy and 11 433 patients received basiliximab induction therapy. The rATG group were younger (53.44 years vs 55.28 years, P < 0.001), more frequently female (58.74% male vs 66.08%, P < 0.001) and more frequently Black (34.78% vs 25.66%, p < 0.001) compared with patients in the basiliximab group.Rejection was more likely with basiliximab compared with rATG at 6 months(OR = 1.64, P < 0.001; 7.81% Basiliximab vs 5.23% rATG)and at 12 months (OR = 1.56, P < 0.001; 8.81% Basiliximab vs 6.31% rATG). Basiliximab induction therapy was associated with worse patient survival, (HR = 1.05, P = 0.017). Basiliximab induction therapy was associated with worse graft survival, (HR = 1.03, P = 0.037). ConclusionThe analysis of the national experience demonstrated favorable rejection, patient survival, and graft survival with rATG usage. Further prospective data are necessary to provide treatment recommendations.

P8.125: Anti-thymocyte Globulin Versus Basiliximab Induction For Kidney Transplantation in Elderly Patients: Matched Analysis With Korean Multicentric Registry

Introduction: Basiliximab (BSX) and anti-thymocyte globulins (ATG), are two major immunosuppressive agents commonly used as induction therapy for kidney transplant (KT) recipients. The superiority of ATG over BSX has not been well established especially in elderly KT recipients with low immunological risk. Method: A total of 847 elderly (≥60 years) low-risk KT patients in the Korean Organ Transplantation Registry were matched with 2:1 propensity scores and compared according to the ATG and BSX induction therapy. The primary outcome was patient and graft survival. The secondary outcome was biopsy-proven rejection, graft function, BK virus nephropathy, infection, cancer, new-onset diabetes mellitus after transplantation (NODAT), and delayed graft function. Results: 165 patients in the ATG group were matched to 298 patients in the BSX group with an average age of 64.3 and 64.2 years, respectively. During 28.5 ± 10.4 months of mean follow up the cumulative probability of death censored graft failure at 3-year posttransplantation were 1.3% and 1.4% in ATG and BSX group without significant difference (p = 0.720). Cumulative probability of NODAT at 3-year posttransplantation was significantly higher in BSX group (35.6% versus 21.6%, p = 0.021). Median Tacrolimus trough level was significantly lower in 6 months after kidney transplantation in the ATG group (5.7 ng/mL versus 6.4 ng/mL, p = 0.001). There was no difference in other evaluated outcomes. Conclusion: Compared to BSX, in elderly low-risk KT, ATG reduced Tacrolimus and steroid requirements without all-cause mortality, rejection, infection difference. Resulting in reduced NODAT incidence.

Antithymocyte globulin versus basiliximab induction for kidney transplantation in elderly patients: matched analysis within the Korean multicentric registry.

BackgroundBasiliximab (BSX) and antithymocyte globulins (ATGs), are two major immunosuppressive agents commonly used as induction therapy for kidney transplant (KT) recipients. The superiority of ATG over BSX has not been well established, especially in elderly KT recipients with low immunological risk.MethodsA total of 847 elderly (≥60 years old), low-risk KT patients in the Korean Organ Transplantation Registry were propensity score-matched at a 1:2 ratio and compared according to ATG or BSX induction therapy. The primary outcome was patient and graft survival and biopsy-proven acute cellular rejection. The secondary outcome was graft function, BK virus nephropathy, infection, cancer, new-onset diabetes mellitus after transplantation (NODAT), and delayed graft function.ResultsIn total, 165 patients in the ATG group were matched with 298 patients in the BSX group with average ages of 64.3 and 64.2 years, respectively. During a follow-up of 28.5 ± 10.4 months, the cumulative probabilities of death-censored graft failure at 3 years posttransplantation were 1.3% and 1.4% in ATG and BSX groups, respectively, without a significant difference (p = 0.72). The cumulative probability of NODAT at 3 years posttransplantation was significantly higher in the BSX group (35.6% vs. 21.6%, p = 0.02). The median tacrolimus trough level was significantly lower at 6 months after KT in the ATG group (5.7 ng/mL vs. 6.4 ng/mL, p = 0.001). There were no differences in the other evaluated outcomes.ConclusionCompared with BSX, in elderly, low-risk KT patients, ATG reduced tacrolimus and steroid requirements without differences in all-cause mortality, rejection, or infection, resulting in a reduced NODAT incidence.

Effect of Redosing Basiliximab in the Setting of Blood Loss in Heart Transplant Recipients on Infection and Rejection

<h3>Purpose</h3> A prior study examining the pharmacodynamics of basiliximab in liver transplant recipients revealed significant medication clearance with blood loss. Dose escalation studies have shown total doses of 40-60 mg are effective and well-tolerated. We sought to examine infection risk when giving a total basiliximab dose of 40 mg vs 60 mg in our heart transplant (OHT) population in the setting of blood loss and requirement of massive transfusion protocol (MTP). <h3>Methods</h3> A single-center retrospective cohort study was performed examining adult OHT patients who received basiliximab induction therapy between June 1, 2010 and October 31, 2019. Cases and controls were matched 1:1. Patients were excluded if they were determined to be immunocompromised prior to transplant. The primary endpoint was incidence of infection. Secondary endpoints included the incidence of cell-mediated or antibody-mediated rejection, as well as the incidence of graft loss within 12 months. <h3>Results</h3> Forty-eight patients who underwent OHT were included, 24 patients in each group (40 mg and 60 mg total dose). Baseline characteristics were similar except for a higher number of LVAD patients in the 60 mg group (16.7% vs 45.8%, p=0.03). A total of 12 patients in the 40 mg group and 18 patients in the 60 mg group experienced at least one infection within 12 months after OHT, although this difference did not meet statistical significance (50% vs 75%, p=0.07). The types of infections were similar between the groups. A stepwise logistic regression showed blood loss and presence of LVAD at the time of transplant were predictors of infection occurrence. Delayed chest closure occurred more frequently in the basiliximab 60 mg group (p=0.002). Acute cellular rejection rates did not differ between groups (p=0.62). Antibody-mediated rejection occurred less frequently in the 40 mg vs 60 mg group (16.7% vs 50%, p=0.03). Two patients experienced graft loss in each group. <h3>Conclusion</h3> In our single-center retrospective study, the administration of an additional dose of basiliximab in the setting of MTP during OHT did not demonstrate a statistically significant increase in the risk of infection nor reduce the risk of rejection. The presence of LVAD at time of transplant was associated with an increased risk of infection and careful consideration should be given to these patients when selecting their induction regimen.

Effects of Reduced-Dose Anti-Human T-Lymphocyte Globulin on Overall and Donor-Specific T-Cell Repertoire Reconstitution in Sensitized Kidney Transplant Recipients.

BackgroundPre-sensitized kidney transplant recipients have a higher risk for rejection following kidney transplantation and therefore receive lymphodepletional induction therapy with anti-human T-lymphocyte globulin (ATLG) whereas non-sensitized patients are induced in many centers with basiliximab. The time course of lymphocyte reconstitution with regard to the overall and donor-reactive T-cell receptor (TCR) specificity remains elusive.Methods/DesignFive kidney transplant recipients receiving a 1.5-mg/kg ATLG induction therapy over 7 days and five patients with 2 × 20 mg basiliximab induction therapy were longitudinally monitored. Peripheral mononuclear cells were sampled pre-transplant and within 1, 3, and 12 months after transplantation, and their overall and donor-reactive TCRs were determined by next-generation sequencing of the TCR beta CDR3 region. Overall TCR repertoire diversity, turnover, and donor specificity were assessed at all timepoints.ResultsWe observed an increase in the donor-reactive TCR repertoire after transplantation in patients, independent of lymphocyte counts or induction therapy. Donor-reactive CD4 T-cell frequency in the ATLG group increased from 1.14% + -0.63 to 2.03% + -1.09 and from 0.93% + -0.63 to 1.82% + -1.17 in the basiliximab group in the first month. Diversity measurements of the entire T-cell repertoire and repertoire turnover showed no statistical difference between the two induction therapies. The difference in mean clonality between groups was 0.03 and 0.07 pre-transplant in the CD4 and CD8 fractions, respectively, and was not different over time (CD4: F(1.45, 11.6) = 0.64 p = 0.496; CD8: F(3, 24) = 0.60 p = 0.620). The mean difference in R20, a metric for immune dominance, between groups was -0.006 in CD4 and 0.001 in CD8 T-cells and not statistically different between the groups and subsequent timepoints (CD4: F(3, 24) = 0.85 p = 0.479; CD8: F(1.19, 9.52) = 0.79 p = 0.418).ConclusionReduced-dose ATLG induction therapy led to an initial lymphodepletion followed by an increase in the percentage of donor-reactive T-cells after transplantation similar to basiliximab induction therapy. Furthermore, reduced-dose ATLG did not change the overall TCR repertoire in terms of a narrowed or skewed TCR repertoire after immune reconstitution, comparable to non-depletional induction therapy.

Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA.

Background: It is still incompletely understood why some patients with preformed donor-specific anti-HLA antibodies (DSA) have reduced kidney allograft survival secondary to antibody-mediated rejection (ABMR), whereas many DSA-positive patients have favorable long-term outcomes. Elevated levels of soluble CD30 (sCD30) have emerged as a promising biomarker indicating deleterious T-cell help in conjunction with DSA in immunologically high-risk patients. We hypothesized that this would also be true in intermediate-risk patients.Methods: We retrospectively analyzed pre-transplant sera from 287 CDC-crossmatch negative patients treated with basiliximab induction and tacrolimus-based maintenance therapy for the presence of DSA and sCD30. The incidence of ABMR according to the Banff 2019 classification and death-censored allograft survival were determined.Results: During a median follow-up of 7.4 years, allograft survival was significantly lower in DSA-positive as compared to DSA-negative patients (p < 0.001). In DSA-positive patients, most pronounced in those with strong DSA (MFI > 5,000), increased levels of sCD30 were associated with accelerated graft loss compared to patients with low sCD30 (3-year allograft survival 75 vs. 95%). Long-term survival, however, was comparable in DSA-positive patients irrespective of sCD30 status. Likewise, the incidence of early ABMR and lesion score characteristics were comparable between sCD30-positive and sCD30-negative patients with DSA. Finally, increased sCD30 levels were not predictive for early persistence of DSA.Conclusion: Preformed DSA are associated with an increased risk for ABMR and long-term graft loss independent of sCD30 levels in intermediate-risk kidney transplant patients.

Rapid Steroid Withdrawal after Renal Transplantation Reduces Mortality: Five Year Follow-Up of a Randomized Controlled Trial (Harmony Study) Confirms Long Term Efficacy and Safety

Background: We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled one year “Harmony” trial, in which 587 predominantly deceased-donor kidney transplant recipients were randomized either to basiliximab or rabbit ATG induction therapy and compared to standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil, and corticosteroids. Methods: Following the end of the original one-year study period, patients were asked to participate in the observational follow-up (FU) study examining most of the end points of the original study. Hereby, de novo incidences between year one and three as well as year three and five were assessed at the three-/five-year visits, respectively. Findings: Biopsy-proven acute rejection and death-censored graft survival rates remained low and independent of RSWD. RSWD was an independent positive factor for patient survival (adjusted hazard ratio 0·554, 95% confidence interval 0·314 to 0·976; p=0·041). Survival rate was increased with 89·4 % or 90·4 % in RSWD patients (basiliximab or rabbit ATG) compared to 84·7 % in control patients (p = 0·064). The reduced incidence of post-transplantation diabetes mellitus in RSWD patients during the original one-year study period was not compensated by later incidences during FU. Also, incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor specific antibody formation, or kidney function did not differ during FU period. Unexpectedly, patient incidences of bacterial infections requiring hospitalization was reduced in the rabbit ATG group. Interpretation: The Harmony FU trial confirms excellent efficacy and beneficial safety aspects of RSWD under modern immunosuppressive therapy. This is the first randomized study demonstrating increased patient survival in RSWD patients. The results shown here support that RSWD should become the new gold standard approach in an immunologically low-risk, elderly, and severely diseased population of Caucasian kidney transplant recipients. Trial Registration: Follow-up study DRK5786; Original trial NCT 00724022). Funding: The FU trial was designed and run by the first and last author who received financial support from Astellas Pharma GmbH and Sanofi (Investigator Initiated Trial (NCT 00724022, follow up study DRK5786). Neither of the funders had any role in data collection, data analysis, data interpretation, or writing of the manuscript. An independent contract research organization (Coordination Center for Clinical Studies of the Technical University of Dresden, Dresden, Germany) was responsible for data collection, monitoring and statistical analyses. Declaration of Interest: CH received grant support, consulting fees, and lecture fees from Astellas, Sanofi, Genzyme, Roche Pharma, Novartis, and Wyeth/Pfizer. CK received consulting fees and lecture fees from Astellas, Chiesi, Novartis, Sanofi-Genzyme. JWM received grant support, consulting fees, and lecture fees from Vifor, GSK, Novartis, Astra-Zeneca and Boehringer Ingelheim. OW has received research grants for clinical studies, speaker’s fees, honoraria and travel expenses from Amgen, Alexion, Astellas, Basilea, Biotest, Bristol-Myers Squibb, Correvio, Chiesi, Gilead, Hexal, Janssen, Dr. F. Kohler Chemie, MSD, Novartis, Roche, Pfizer, Sanofi, Takeda, TEVA and UCB. BB received grant support, consulting fees and lecture fees from Astellas, Bayer, Chiesi and Novartis. All other authors declare no competing interests. Ethical Approval: The study was approved by the institutional review boards of all sites participating in the follow-up period.

Post-transplant absolute lymphocyte count predicts early cytomegalovirus infection after heart transplantation

Immunosuppressive therapy can decrease rejection episodes and increase the risk of severe and fatal infections in heart transplantation (HT) recipients. Immunosuppressive therapy can also decrease the absolute lymphocyte count (ALC), but the relationship between early post-transplant ALC and early cytomegalovirus (CMV) infection is largely unknown, especially in HT. We retrospectively analyzed 58 HT recipients who tested positive for CMV IgG antibody and received basiliximab induction therapy. We collected preoperative and 2-month postoperative data on ALC and CMV load. The CMV load > 1200 IU/mL was used as the cutoff value to define early CMV infection. Post-transplant lymphopenia was defined as an ALC of < 500 cells/μL at postoperative day (POD) #7. On POD #7, 29 (50.0%) patients had post-transplant lymphopenia and 29 (50.0%) patients did not. The incidence of CMV infection within 1 or 2 months of HT was higher in the post-transplant lymphopenia group than in the non-lymphopenia group (82.8% vs. 48.3%, P = 0.013; 89.7% vs. 65.5%, P = 0.028, respectively). ALC < 500 cells/μL on POD #7 was an independent risk factor for early CMV infection within 1 month of HT (odds ratio, 4.14; 95% confidence interval, 1.16–14.77; P = 0.029). A low ALC after HT was associated with a high risk of early CMV infection. Post-transplant ALC monitoring is simple and inexpensive and can help identify patients at high risk of early CMV infection.

Opportunistic Infections After Induction With Alemtuzumab or Basiliximab: A 3-Year Kidney Transplantation Experience

BackgroundAntibody induction immunosuppression is commonly used in kidney transplantation to decrease the risk of early acute rejection. However, infectious complications may arise in patients treated with higher intensity induction immunosuppression. In this study, we compared the rate of opportunistic infections during the 3 years after kidney transplantation in recipients who received either alemtuzumab or basiliximab for induction therapy. MethodsAll renal transplant recipients from our center who received induction with alemtuzumab between 2011 and 2016 were included and matched 1:2 (by age and date of transplant) to renal transplant recipients who received basiliximab. The primary outcome was the rate of opportunistic infections. ResultsTwenty-seven patients received alemtuzumab (mean age = 50.8 years; SD ±12), and 54 received basiliximab (mean age = 50.8 years; SD ±11.8). Infections within 3 years posttransplant were not different between groups: BK viremia (P = .99), BK nephritis (P = .48), cytomegalovirus infection (P = .13), varicella zoster virus (P = .22), and all infections (P = .87). Time to infection (P = .67), patient survival (P = .21), and time to rejection (P = .098) were similar in both groups. There were also no group differences in delayed graft function (P = .76), graft loss (P = .97), or rejection (P = .2). ConclusionThe rate of infection was not significantly increased in recipients receiving lymphocyte-depleting alemtuzumab compared to recipients receiving basiliximab induction therapy, despite receiving similar maintenance immunosuppression. Although the immunologic risks differed between the 2 groups, there was no observable difference in clinical outcomes.

Evaluation of Targeted Basiliximab Induction Therapy in Lung Transplant

Antibody induction therapy has been shown to reduce acute rejection episodes in organ transplantation. Universal basiliximab (BAS) induction therapy was discontinued at our center due to lack of efficacy versus no induction. Targeted induction therapy with BAS was developed for patients with acute kidney injury. This study compares the incidence of acute and chronic rejection in lung transplant (txp) recipients who received basiliximab for acute kidney injury (AKI). Patients transplanted between 2008-2018 were retrospectively divided into two groups (grps): (1) BAS vs (2) no induction. Maintenance IS included a calcineurin inhibitor, mycophenolate or azathioprine, and prednisone. Acute rejection (AR) was defined as ISHLT grade A2 or greater. Variables examined included baseline characteristics, incidence of AR, infections within 12 months (mo), serum creatinine (Scr) pre- and post-txp, antibody mediated rejection, post-transplant lymphoproliferative disorder (PTLD), time to CLAD development, and patient survival. 318 patients qualified for analysis: 59 patients received BAS. The groups were comparable in regards to gender, age, diagnosis, and CMV status. Grp 2 had more single transplants (p= 0.032). Overall, AR at 12 mo was similar in both groups (15.6% vs. 19.6%, p=NS). Pre-txp Scr and Scr at 30 days post-txp were similar in both groups. Freedom from CLAD was similar in both groups at 2 years (grp 1= 36 v. grp 2= 178 pts, p= 0.163). No difference was observed between the groups regarding secondary outcomes shown in the table. However, patients receiving BAS therapy trended toward worse survival at 12 mo when compared to no induction. In conclusion, our single-center experience demonstrated similar outcomes in patients with AKI who received targeted basiliximab induction therapy in conjunction with delayed calcineurin inhibitor initiation.

Low-dose Thymoglobulin vs Basiliximab Induction Therapy in Low-Risk Living Related Kidney Transplant Recipients: A Prospective Randomized Trial

ContextThymoglobulin is used effectively as induction agent in kidney transplantation but the optimal dose is not well established. ObjectiveDemonstrate that low-dose thymoglobulin (3 mg/kg) has similar efficacy and safety compared to basiliximab induction in low-risk kidney transplantation under standard maintenance immunosuppression Design, Setting, ParticipantsProspective randomized study in kidney transplant patients (12/2016-05/2018). Inclusion criteria: Recipients > 18 years, first living donor transplant. Exclusion criteria: Second and multiorgan transplant, ABO incompatibility, positive cross-match, panel reactive antibodies (PRA) > 30%, positive donor-specific antibody, human immunodeficiency virus, hepatitis B surface antigen, hepatitis C virus positive, white blood cells < 2000 cells/mm3, platelets < 75,000 cells/mm3 and malignancy. InterventionGroup A: basiliximab (20 mg D0 and D4). Group B: thymoglobulin (3 mg/kg total). Maintenance immunosuppression: tacrolimus, mycophenolate mofetil, and steroids. Main Outcome MeasuresBiopsy-proven acute rejection (BPAR), delayed graft function, slow graft function, leukopenia, infections, adverse events, graft loss, estimated glomerular filtration rate, and death within 12 months. Results100 patients (basiliximab, n = 53) (thymoglobulin, n = 47) were included. Donor and recipient characteristics were similar except for longer dialysis (basiliximab), PRA class I (1.2% basiliximab, 4.5% thymoglobulin), HLA match (basiliximab 2.8, thymoglobulin 2.2), and cytomegalovirus status. BPAR rate was basiliximab 3.8% and thymoglobulin 6.4% (P = ns). Delayed graft function (basiliximab 3.8%; thymoglobulin 4.3%), slow graft function, and 12-month leukopenia (basiliximab 11.3%, thymoglobulin 21.3%) were similar between groups (P = ns). There was no difference in infections and adverse events between groups. Patient and graft survival were as follows: basiliximab 98.1% and 92.5%, thymoglobulin 100% and 93.6% (P = ns). ConclusionLow-dose thymoglobulin induction (3 mg/kg) can be used effectively and safely in low-risk kidney transplantation with good results during the first year post-transplant.

Long-term outcomes of pediatric kidney transplantation: A single-center experience over the past 34years in Japan.

To evaluate long-term outcomes and risk factors for graft loss in pediatric kidney transplantation over a 30-year period. We retrospectively assessed 400 consecutive kidney transplants carried out in 377 children during 1975-2009. Patients were stratified according to the immunosuppressive regimen (era1: methylprednisolone and azathioprine; era2: calcineurin inhibitor-based therapy, including methylprednisolone and azathioprine or mizoribine; era3: basiliximab induction therapy, including calcineurin inhibitors, methylprednisolone and mycophenolate mofetil). The median age and bodyweight at transplantation were 9.7years and 20.6kg, respectively. In total, 364 (91.0%) children received a living related donor transplantation. The acute rejection rate within 1year post-transplant decreased significantly from 61.0% in era1 to 14.5% in era3 (P<0.001). For transplant eras1-3, 1-year graft survival was 81%, 93% and 95%; 5-year graft survival was 66%, 86% and 93%; and 10-year graft survival was 47%, 79% and 89%, respectively. The overall 5-, 10- and 20-year patient survival rates were 96%, 93% and 88%, respectively. A Cox multivariate analysis identified cold ischemia time (hazard ratio 1.385, 95% confidence interval 1.251-1.603), acute rejection (hazard ratio 1.682, 95% confidence interval 1.547-3.842), re-transplant (hazard ratio 2.680, 95% confidence interval 1.759-3.982) and donor type (hazard ratio 2.957, 95% confidence interval 1.754-4.691) as independent risk factors for graft loss at 10years post-transplant. The progress of immunosuppressive therapy has led to a low incidence of acute rejection and a high graft survival rate across 30years of pediatric transplantation.

Effectiveness of Thymoglobulin Induction Therapy in Kidney Transplant From Deceased Donor With Mild to Moderate Acute Kidney Injury

BackgroundThe clinical benefit of rabbit antithymocyte globulin (Thymoglobulin) compared with basiliximab for induction therapy in kidney transplant (KT) resulting from acute kidney injury (AKI) donors remains controversial. In cases of severe AKI, the degree of kidney injury is too great to reveal influence of different induction therapies on clinical outcomes. We aimed to compare clinical outcomes of Thymoglobulin and basiliximab induction therapy in KTs from deceased donors (DDs) with mild to moderate AKI. MethodsWe retrospectively studied 147 patients who received KTs from DDs between 2009 and 2017 in our center; 91 patients received kidneys from AKI donors. The AKI severity was classified based on the Acute Kidney Injury Network (AKIN) staging, and patients with AKIN stage 3 (43 patients) were excluded. Clinical outcomes were compared according to the type of induction therapy. ResultsThymoglobulin and basiliximab induction groups showed no significant differences in demographic and baseline characteristics except donor age and follow-up period. The Thymoglobulin group had lower incidences of acute rejection and a trend toward a lower incidence of delayed graft function and better graft survival than the basiliximab group. There was no significant difference in BK infection rate; however, cytomegalovirus infection rate showed a trend toward a lower incidence in the basiliximab group. ConclusionsIn cases of KT from AKIN stage 1 and 2 donors, Thymoglobulin showed better clinical outcomes than basiliximab, although it had a somewhat high rate of cytomegalovirus infection. It seems beneficial to use Thymoglobulin induction therapy in KTs from DDs with mild to moderate AKI.